Enterocyte-innate lymphoid cell crosstalk drives early IFN-γ-mediated control of Cryptosporidium
Authors list
Jodi A Gullicksrud Adam Sateriale Julie B Engiles Alexis R Gibson Sebastian Shaw Zachary A Hutchins Lindsay Martin David A Christian Gregory A Taylor Masahiro Yamamoto Daniel P Beiting Boris Striepen Christopher A HunterAbstract
The intestinal parasite, Cryptosporidium, is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance to Cryptosporidium, which specifically invades enterocytes, is dependent on the production of IFN-γ, yet whether enterocytes contribute to parasite control is poorly understood. In this study, utilizing a mouse-adapted strain of C. parvum, we show that epithelial-derived IL-18 synergized with IL-12 to stimulate innate lymphoid cell (ILC) production of IFN-γ required for early parasite control. The loss of IFN-γ-mediated STAT1 signaling in enterocytes, but not dendritic cells or macrophages, antagonized early parasite control. Transcriptional profiling of enterocytes from infected mice identified an IFN-γ signature and enrichment of the anti-microbial effectors IDO, GBP, and IRG. Deletion experiments identified a role for Irgm1/m3 in parasite control. Thus, enterocytes promote ILC production of IFN-γ that acts on enterocytes to restrict the growth of Cryptosporidium.
Journal details
Journal Mucosal Immunology
Volume 15
Issue number 2
Pages 362-372
Available online
Publication date
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Publisher website (DOI) 10.1038/s41385-021-00468-6
Europe PubMed Central 34750455
Pubmed 34750455
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